tbuckley/cabot-search huggingface dataset:
National lung cancer screening rates among women veterans within the Veterans’ Health Administration.
Authors: Jennifer Bail, Ajitha Kommalapati, John Dell'Italia, Devika Govind Das
Journal: Journal of Clinical Oncology (2023)

1543 Background: Lung cancer is the number one cause of cancer related death among women in the United States. United States Preventive Services Task Force (USPTF) lung cancer screening (LCS) guidelines recommend annual low dose computed tomography (LDCT) among high-risk populations. The data specifically on women veterans is sparse so we retrospectively examined LCS rates among women veterans within the VHA. Methods: Women veterans ages 50-80, current or former (quit within 15 years) smokers from 2013- 2021 were identified through the VA corporate data warehouse (CDW). Captured characteristics included: demographics, smoking history, and cancer screening history (lung, breast, cervical). Data was analyzed using R Studio software. Results: Women veterans with a history of smoking (n=40,299) tended to be aged ≥60, white (66%), single (69%), unemployed (64%), urban dwelling (67%), and residing in Southeast U.S. (31%). Overall, cancer screening rates among women veterans was low (9% lung; 27% breast; 21% cervical). Of the women not screened for lung cancer (91%; n=36,837), 11% (n=4, 016) had a personal history of cancer. While pack-year history was not documented for the vast majority (92%), 7% (n= 2, 729) reported a &gt;30 pack-year smoking history (guideline at the time). Of these &gt;30 pack-year smokers, 88% (n=2,418) were not screened for lung cancer. Other significant demographic predictors of increased LCS rates included Southeast Veterans Integrated Service Network (VISN region) and comorbidities such as bipolar disorder and diabetes likely due to increased exposure to healthcare. Conclusions: LCS rates, as well as breast and cervical, among women veterans within the VHA is low. The lack of documented pack-year history among women veterans with a history of smoking is concerning. Increased documentation of pack-year history may aid in identifying women for LCS. Efforts are ongoing nationally to implement an equitable centralized LCS program for all veterans and as part of that effort the Birmingham VA Health Care System has utilized their Lung precision Oncology program (LPOP) funding to pilot a structured lung cancer screening program within our Women’s Health Clinic in 2022.
Delivery of precision oncology in advanced lung cancer: Gaps, barriers, and potential solutions.
Authors: Jacob Newton Stein, Mary E. Grewe, Alayah Johnson-Jennings, Courtney Canter, Marjory Charlot
Journal: Journal of Clinical Oncology (2023)

e13533 Background: Non-small cell lung cancer is the leading cause of cancer death. Significant survival gains have been achieved due to precision oncology, which involves testing for molecular markers that indicate sensitivity to targeted therapies. Precision oncology is essential to high-quality lung cancer care, but shortfalls in biomarker testing and targeted therapies limit improvements in lung cancer outcomes. We sought to characterize barriers and facilitators to precision oncology in academic and community practice settings. Methods: We conducted a mixed methods study on the delivery of precision medicine for patients with advanced lung cancer, including use of next generation sequencing (NGS), liquid biopsy, and targeted therapies, and the barriers and facilitators to effective delivery. Surveys and semi-structured interviews were conducted with a purposive sample of patient navigators, pathologists, and clinicians. Participants were recruited from community and academic settings in North Carolina (NC), using the NC Oncology Navigation Association and existing research networks. Results: Thirty-two participants completed the survey—9 navigators, 10 pathologists and 13 clinicians—with representation from community and academic sites. Five participants completed interviews—2 navigators, 2 pathologists and 1 clinician. Knowledge gaps about precision medicine were observed, with clinicians answering “not at all” or “a little bit” knowledgeable about NGS (23%), liquid biopsy (38%) and targeted therapies (23%). Navigators indicated feeling “somewhat” or “very” uncomfortable discussing these topics (55% for NGS, 44% for targeted therapies), and indicated having limited confidence in resolving barriers related to precision medicine. In interviews, potential solutions were highlighted, including use of financial aid from pharmaceutical companies, dedicated molecular pathology support, and partnership with social work and financial navigation to resolve barriers. Conclusions: Clinicians and navigators report gaps in knowledge and confidence in discussing precision oncology in advanced lung cancer. Qualitative data highlight several potential strategies for improving access, including addressing financial barriers. These findings suggest a need for education and financial assistance to support delivery of precision oncology in advanced lung cancer.[Table: see text]
A preclinical study to evaluate the combination of azeliragon, an inhibitor of the receptor for advanced glycation endproducts (RAGE), with radiation therapy as a potential treatment of glioblastoma.
Authors: Subhajit Ghosh, Jiayi Huang, Dennis Hallahan, Stephen Garrett Marcus, Dinesh Thotala
Journal: Journal of Clinical Oncology (2023)

e14056 Background: Systemic lymphopenia, which is independently associated with poor overall survival, is observed in approximately 30-50% of patients with glioblastoma (GBM) after chemoradiotherapy. We recently found that cranial irradiation of GBM tumors increases circulating myeloid-derived suppressor cells (MDSC) contributing to systemic lymphopenia. Additionally, we found that cranial radiation increases circulating levels of the RAGE ligands S100A8/9 and HMGB1, which have been reported to increase MDSC and their immunosuppressive effects through binding RAGE. We, therefore, hypothesized that targeting RAGE receptors on MDSC could prevent immunosuppression and improve survival in preclinical GBM models. Methods: We orthotopically implanted GBM cells (GL261 and CT2A) into immunocompetent C57BL6 mice. The GBM tumor-bearing mice were treated with five doses of fractionated radiation therapy (RT, 2 Gy/day for 5 consecutive days) to the whole head in combination with RAGE inhibitor azeliragon (0.1mg/mice/day i.p starting one day before RT for up to 10 days). We evaluated the immune cells in the tumor microenvironment (TME) and spleen at 14 days post-tumor implantation. We also evaluated the circulating immune cells and RAGE ligands (HMGB1 and S100A8/A9) in the plasma at 7, 14, and 21 days post-tumor implantation and monitored the mice for survival up to 60 days. Results: GBM tumor-bearing mice (GL261 &amp; CT2A) treated with RT plus azeliragon had significantly improved survival when compared to RT alone or azeliragon alone. RT plus azeliragon significantly reduced the accumulation of granulocytic-MDSC (G-MDSC), monocytic-MDSC (M-MDSC), tumor-associated macrophages (TAM), and regulatory T cells (T reg ), while increasing infiltrating CD8 T cells in the TME as compared to RT alone. RT alone significantly increased the accumulation of G-MDSC and M-MDSC in the spleen, which was significantly reduced with concurrent azeliragon. Concurrent administration of azeliragon with RT did not significantly affect the radiation-induced increase of circulating M-MDSC as well as plasma HMGB1 and S100A8/A9 concentration, though there was a modest reduction of circulating G-MDSC. Conclusions: Our study indicates that azeliragon, by blocking RAGE interaction with its ligands, helps to overcome the MDSC-mediated immunosuppression that occurs after RT. The combination of azeliragon with RT enhances survival in preclinical models. Clinical trials evaluating the safety and efficacy of azeliragon in combination with RT for newly diagnosed GBM are currently under development.
Ventriculoperitoneal shunt and performance status as prognostic factors of overall survival in a retrospective cohort of 78 adult patients with medulloblastoma.
Authors: Raul Rogelio Trejo-Rosales, Dulce Angelica De Jesus Hernandez, Daniela Castro Merida, Juan Carlos Silva Godinez, Andrea Otamendi-Lopez, Yuly Andrea Remolina Bonilla
Journal: Journal of Clinical Oncology (2023)

e14062 Background: Adult medulloblastoma (AM) is a rare disease and represents 1 % of CNS tumors with an incidence of 0.6 per million per year. Usually arise in the cerebellar hemisphere or dorsal brainsteam. Four molecular subgroups are widely recognized and SHH subgroup are common in AM. Treatment options are usually extrapolated from pediatrics experience, and involve surgical resection followed by radiotherapy +/- chemotherapy. Methods: We conducted a retrospective cohort study in patients with medulloblastoma aged ≥18 years at a tertiary institution in Mexico City. We aim to describe clinical and treatment patterns predicting OS and PFS in an adult cohort of medulloblastomas. Kaplan Meier and Log-rank methods were used for survival analysis. Cox proportional hazard model was used for multivariate analysis. Results: Between 2010 and 2022, 78 patients met the criteria for this study. The median age was 28 years (range 18-62) and 64.1% were men. A total of 75.6% had ECOG 0-1. The desmoplastic was the most frequent histologic variant (35.9%). Surgical resection was performed in 93.6% with R0 resection in 49.3% (n=36), while 76.9% (n=61) underwent ventriculoperitoneal shunt (VPS). A total of 70 pts (89.7%) received adjuvant radiotherapy (RT), and the median time to initiation was 18 weeks. Adjuvant and concurrent chemotherapy were received in 53.8% and 12.8%, respectively. One-third of patients did not receive chemotherapy. Vincristine, cisplatin, and cyclophosphamide was the most common combination chemotherapy regimen (28.5%). PFS and OS in the entire cohort were 27.9 months (mo) (95% CI 9.9-45.9) and 124.3 mo (95% CI 52.8-59.8), respectively. OS in patients with ECOG 0-1 was better with 144.8 mo compared with 51.5 mo for ECOG 2-3 (p&lt;0.001). Patients receiving adjuvant RT survived significantly longer (124.3 mo) than patients without radiation (18.8 mo). Other factors associated with survival were time to RT initiation ≤18 weeks vs &gt;18 weeks (not reached vs 59.1 mo, p=0.018) and VPS insertion (144.8 mo vs 46.5 mo, p=0.023). Multivariate analysis identified performance status such as ECOG 2-3 (HR 2.93; 95% CI 1.3-6.6, p=0.009) and VPS (HR 0.39; 95% CI 0.16-0.93, p=0.034) as independent prognostic factors for OS. Conclusions: in this large cohort of Adult Medulloblastoma, we identified ventriculoperitoneal shunt and performance status as the most important factors related with better survival outcomes.
Incidence of interstitial lung disease and cardiotoxicity with trastuzumab-deruxtecan in patients with breast cancer: A systematic review and single-arm meta-analysis.
Authors: Leonardo Ribeiro Soares, Victor Domingos Lisita Rosa, Maysa Vilbert, Jessica Lopes Oliveira, Mariana Moreira Deus, Ruffo Freitas-Junior
Journal: Journal of Clinical Oncology (2023)

e13033 Background: The new antibody-drug conjugated directed to HER2, Trastuzumab-Deruxtecan (T-DXd), has shown the benefit of progression-free survival and overall survival in metastatic breast cancer (mBC) patients after progression to ≥1 HER2 targeted therapies. Interstitial lung disease (ILD) and cardiotoxicity are the most significant and concerning toxicities related to T-DXd. We performed a systematic review and meta-analysis to assess the incidence and severity of those adverse events (AE) in mBC patients treated with T-DXd. Methods: We comprehensively searched Pubmed, Cochrane, and Scopus databases for randomized clinical trials (RCT) and observational cohort studies, including mBC patients with HER2-low or -positive expression who have received at least one dose of T-DXd. The DESTINY-Breast02 study was also included after its presentation at the SABCS 2022. The statistical analysis was performed using R software, and the results are presented as pooled analysis in forest plots. Results: We included nine studies: three phase III RCTs, three phase II and two phase I non-RCTs, and one retrospective cohort comprising 1,443 patients with a mean follow-up of 14.9 months. The median age of our population ranged from 53 to 59 years. Most were non-Asian (40.5%) and presented with hormone-receptor positive mBC (66.8%). In a pooled analysis, the incidence of ILD was 13.0% (179 patients; 95%CI 11.0 to 13.0). Patients enrolled in phase III clinical trials had an ILD rate of 12.0%, while the observational cohort reported a numerically higher rate of 18.0%. Most ILD cases, 84.9% (152 patients), were mild (grade 1 or 2). Grade 3 or 4 AE were reported in 13 patients (7,3%), and grade 5 in 14 patients (7,8%). Decreased left ventricular ejection fraction (LVEF) was seen in 3.6% (95%CI 3.0 – 5.0%), and most patients were asymptomatic. Eleven patients developed prolonged QT interval, and four had left ventricular dysfunction and cardiac failure. Conclusions: Our meta-analysis reinforces the importance of close vigilance for pulmonary and cardiac toxicities in mBC patients on treatment with T-DXd. Early detection and management by a multidisciplinary team following the most recent guidelines may improve the patient outcomes. [Table: see text]
Improving compliance with post-hospitalization follow-up visits: A single community cancer center experience.
Authors: Tejaswi Venigalla, Manasa Anipindi, Dhaval Patel, Mark S. Morginstin
Journal: Journal of Clinical Oncology (2023)

e13508 Background: Hospital discharge follow-up visits are crucial for the continuity of care and for reducing rehospitalizations. They prevent medication disruptions, missing opportunities for making a post-discharge treatment plan, and identifying complications. Our aim is: 1. To review the compliance of post-hospitalization follow-ups for a medical specialty. 2. To study the timeline from the discharge to the time they were seen in the hematology-oncology clinic. 3. To identify why patients seen in the hospital were lost to follow-up. 4. To improve compliance with post-discharge follow-up visits. Methods: This is a retrospective chart review of patients seen by our Hematology-oncologists at Einstein Medical Center Montgomery between January 2021 to December 2021. Data collected included: Specialty consulted- Hematology versus Oncology; if follow-up is indicated; if they have a Hematology Oncology provider elsewhere; if they were seen in the clinic and how long did it take for the patient to be seen after discharge; if they did not follow-up, the reason for failure to follow-up was reviewed. We defined “No contact from our office” when there was no documentation that our office staff tried to contact the patient to make a follow-up appointment. Results: Out of the total 526 inpatient consultations, 338 were for hematology, 169 were for oncology and 19 were for both hematology and oncology. Follow-up upon discharge was recommended for 429 patients (82%). Out of those 429 patients, 168 patients (39%) were seen in the clinic and 176 patients (41%) were not seen after discharge from the hospital. 85 patients (20%) had a Hematology Oncology provider in a different institution. 118 patients (68%) in this group of 168 patients were seen in less than 30 days. 41% of the patients that were not seen after discharge from the hospital had various reasons, which included 18% of patients who expired, and 10% of patients who chose to be on comfort care. 41% of the patients were lost to follow-up (unable to track after the discharge – data was limited due to this being a retrospective study), 2% of the patients were incarcerated, 23% of the patients had no contact from our office to make a follow-up appointment, 1% of the patients were subsequently hospitalized, and finally, 5% of the patients followed up in a different institution. Conclusions: Hematology was consulted more often than Oncology for the subspecialty in-hospital consultations. 41% of the patients were lost to follow-up due to reasons unknown who should have been seen in the Hematology/Oncology Clinic. Interventions that we recommend in improving this compliance are 1. Formulate a rapid discharge clinic – run by Hematology-Oncology fellows with attending oversight. 2. Involve the Oncology Nurse Navigator to help coordinate patient follow-up. 3. Provide better education for hospital staff about the importance of reviewing discharge instructions with the patients.
Intraoperative glioma characterization using time-resolved fluorescence spectroscopy.
Authors: Simon Menaker, Chirag Patil, Kamil Krawczyk, Ray M. Chu, Adam N. Mamelak, Serguei I. Bannykh, Jethro Lisien Hu, Keith L. Black, Pramod V. Butte
Journal: Journal of Clinical Oncology (2023)

2072 Background: Extent of surgical resection significantly improves progression-free and overall survival in glioma patients. Due to the infiltrative nature of gliomas, tumor margin detection is often difficult, and current intraoperative visualization methods are limited. Time-resolved fluorescence spectroscopy (TRFS) has the potential of differentiating glioma from normal brain tissue, thereby maximizing extent and safety of resection. Methods: Twenty-seven preoperative patients diagnosed with glioma met inclusion criteria for an IRB-approved study aimed to assess the accuracy of TRFS relative to tissue histopathology for differentiating glioma from normal cortex (NC), normal white matter (NWM), and white matter with edema (WME). A multi-channel TRFS system was developed for in vivo brain tissue and tumor characterization during glioma surgery. A custom-designed fiber optic probe was used to deliver ultrafast laser pulses to tissue regions of interest and collect fluorescence signals, with simultaneous registration to intraoperative neuronavigation. The fluorescence light was collected using a photomultiplier tube and digitized across six wavelength bands. Biopsies were taken at each measurement site for evaluation by a blinded neuropathologist to determine the accuracy of TRFS, which was calculated using parameters derived from the recorded fluorescence pulse and used to characterize tissue signatures. Results: During surgical resection of 27 patients, 162TRFS measurements were collected in vivo followed by biopsy of the same tissue. Samples from brain tumors (39 low grade gliomas (LGG, WHO grade I to III), 35 high grade gliomas (HGG, WHO grade IV)) were compared with 47 samples of normal brain tissue (NC and NWM). The time-resolved system was able to differentiate LGG from normal tissue with 97% sensitivity and 93% specificity (93% PPV and 98% NPV). When all tumor grades were tested, the sensitivity dropped to 91% (96% PPV and 86% NPV), which we believe reflects the heterogeneity of HGG. HGG alone showed a sensitivity of 83% and specificity of 93% (91% PPV and 88% NPV). Normal cortex had the fastest decays across all wavelength bands among different tissue types, WME had longer decays compared to other tissue types at all wavelengths, and HGG had a variable but predictably different fluorescence decay pattern. Conclusions: TRFS is an intraoperative tool that can distinguish glioma from normal brain tissue and has the potential to maximize safe surgical resection.
Distribution of alternate site infusion providers in the US.
Authors: Cindy Revol, Catherine Patton, Sanjula Jain, Allison H Oakes
Journal: Journal of Clinical Oncology (2023)

1542 Background: Spurred by the pandemic, chemotherapy treatments provided by alternate site infusion providers have been increasing. This diversification has the potential to increase access to care and improve patient satisfaction. However, it is currently unknown how equitably distributed these non-traditional infusion settings are, and whether these newer entrants are entering markets with need or markets with ample supply. In addition, many community oncologists are concerned about the ability to retain control over a patient’s treatment and preserve the profits earned from drug infusions. Further, there are concerns regarding the lack of robust data on the safety of alternate site chemotherapy infusions. Industry analysts anticipate steady expansion in US markets for alternate site infusion with chemotherapy being a strong driver of growth. The objective of this study was to examine the distribution of alternate site infusion services across the US. Methods: Leveraging the Medicare home health infusion (MHHI) provider database from CMS, we calculated the rate of MHHI providers per 1000 Medicare beneficiaries in each US state. We reviewed company information to determine the geographic footprint of 3 alternate site infusion providers. Results: The median MHHI rate was 0.013 per 1000 beneficiaries (CO), the average rate was 0.031, with a minimum of 0 (ND, SD, WY) and a maximum of 0.202 (IL). ND, SD, WY, IN, KY, and OK have the lowest concentration of MHHI providers, whereas OR, KS, WA, NE, CA, and IL have the highest concentration. 3 alternate site infusion providers are Option Care, UnitedHealth’s Optum Infusion Pharmacy, and Coram, CVS Specialty Infusion Services. Option Care has 162 in-person infusion centers located in 45 states. Option Care’s presence is highest in CA (24), FL (9), WA (9), OH (8), VA (8), and TX (7). UnitedHealth’s Optum Infusion Pharmacy has 30 in-person infusion suites located in 20 states, primarily concentrated in FL (6) and CA (4), but also provides home infusions in all 50 states. Like MHHI providers, neither of these alternate-site providers have locations in ND, SD, or WY. Coram announced a pilot with Cancer Treatment Centers of America in 2021 to provide home chemotherapy to patients in GA, but it is unclear if that pilot is ongoing; Coram provides home infusion therapy in 49 states. Conclusions: MHHI and alternate site infusion providers are in markets across the US. If alternate site chemotherapy infusion continues to grow, health system-owned and 3rd party entrant alternate site infusion providers are likely to prosper. Conversely, physician-owned practices could face competition and loss of important drug infusion revenue leading to increased consolidation among independent oncology providers. More research is needed to determine the impact on cost and patient outcomes of alternate site chemotherapy infusions – insights that will impact reimbursement and the rate at which these services continue to grow.